The etiologic role of dihydrocortisol in the sensitivity of primary open angle glaucoma (POAG) patients to the intraocular pressure (IOP) raising effects of glucocorticoids and in the ocular hypertension characteristic of this disorder, is suggested by three lines of evidence. The first is the ability of the metabolite to potentiate the IOP raising effects of dexamethasone in young rabbits, the second is the accumulation in vitro of large quantities of dihydrocortisol(s) in cells cultured from trabeculectomy specimens from patients with POAG AND THE THIRD IS THE PRELIMINARY FINDING OF THE PRESENCE OF THESE METABOLITES IN SERUM OR AQUEOUS HUMOR IN 5 OUT OF 7 PATIENTS WITH POAG. The present investigation is designed to complete the development of sensitive and specific radioimmunoassays to measure both 5 alpha and 5 beta- dihydrocortisol in ocular and nonocular fluids (aqueous humor, tears, saliva and serum) in POAG and nonPOAG patients. The presence of dihydrocortisol(s) in POAG would provide direct support for the hypothesis that abnormal cortisol metabolism is related to this disorder and permit determination of the prevalence of this abnormality in POAG independent of cell culture methodologies. Furthermore, the presence of dihydrocortisol(s) in the more readily obtainable fluids (tears, saliva or serum) may serve as a marker for patients at risk for this disease and suggest new therapeutic modalities.